CONFERENCE REPORT 732

CHIMIA 2001, 55, No.9

CONFERENCE REPORT

Chimia 55 (2001) 732-736 © Schweizerische Chemische Gesellschaft ISSN 0009-4293

Selective Synthesis: New Reagents for Specific Transformations Champery, June 6-9, 2001

Christian G. Bochet*

Keywords: CERC3 . Champery . European chemistry' Organic synthesis· Workshop

The chairmen of the European Re- from the chiral centers, had a strong im- The day was concluded with the first search Councils' Chemistry Committees pact on the geometry of the dimeric cata- plenary lecture, by Professor Varinder (CERC3) elected organic synthesis as lyst; these effects could be so strong that Aggarwal (University of Bristol, UK). this year's topic for their annual work- similar catalysts varying only by one sub- He explained the asymmetric epoxida- shop, and Switzerland as the host coun- stituent gave opposite enantiomers [1]. tion reaction, in which, instead of using try. The conference chairman, Prof. The afternoon session was concluded the classical strategy (i.e. oxidation of an Philippe Renaud made the excellent by Petri Pihko (The Scripps Research In- alkene), the key step is a carbon-carbon choice of Champery for hosting the stitute, La Jolla, USA), on the synthesis bond forming process (the so-called Co- workshop; the combination of his enthu- of Azaspiracid (Fig. 1), a very potent tox- rey-Chaykovsky epoxidation). The beau- siasm, efficient organization and the in, isolated from Irish mussels. The FGHI ty of this reaction, very simple in its ex- beautiful alpine scenery made this meet- spirocyclic portion proved to be a very perimental realization, is revealed by the ing a really unique event. Its success challenging pattern to assemble, particu- intricate catalytic cycles orchestrated like clearly arose from the scientific program, larly with the presence of acid-sensitive clockwork. Detailed mechanistic studies, which was particularly exciting. Thirty- ketal groups. After several attempts at re- including catalyst structure/activity rela- one half-hour lectures from young chem- designing the route without success, tionships and computational modeling ists, mostly at the beginning of their inde- Pihko showed how the azaspiro moiety were presented to rationalize the origin of pendent research careers were comple- the enantioselectivity. In the last part of mented by three plenary lectures from his lecture, Aggarwal showed that this re- prominent, established professors in Eu- action was not limited to epoxidation, but rope. can be applied also to aziridination or The first lecture was given by Bernd cyc1opropanation [3]. Goldfuss (University of Heidelberg, Ger- HO Transition metal asymmetric catalysis many), focusing on the use of modular was central to the first part of the Thurs- fencholates as probes for studying the day morning session, starting with enantioselective addition of organozinc Giuseppe Mantovani (IS SEC Firenze, reagents to benzaldehyde. High-level Italy). The methoxycarbonylation of sty- computational modeling of the transition rene (i.e. the reaction of styrene with car- Azaspiracid structure revealed that subtle changes of bon monoxide and methanol) was inves- substituents on the ligand, even remote tigated under Pd catalysis with various Fig. 1 phosphorous ligands. It was found that was eventually prepared efficiently. The small changes in the ligand structure in- 'northern part' ABCDE proved to be just duced dramatic changes in the reaction as challenging; despite intensive efforts, outcome. For example, the classical 'Correspondence: Dr. e.G. Bochet to date, it has only been partially pre- Pd(dppe)(MeCNh yielded exclusively Department of Organic Chemistry methyl cinnamate (the expected product), University of Geneva pared. These synthetic problems show 30 quai Ernest-Ansermet once again that total synthesis remains an whereas a dimeric analogue of 2,3-dppd CH-1211 Geneva 4 art, and that it should not be taken for (1,2,3,4 tetrakis(diphenylphosphino) cy- Tel.: +41 227026288 Fax; +41 22 328 73 96 granted that any molecule can now be c1obutane) led mainly to the formation of E-Mail: [email protected] easily synthesized [2]. dimethyl phenyl succinate [4]. CONFERENCE REPORT 733 CHIMIA 2001, 55, NO.9

The field was then expanded by Si- with the preparation of heterocyclic ana- ical translocation, where the halide is lo- mon Breeden (National University of logues of rubicene. These molecules cated on the aromatic ring (e.g. in a 0- Ireland, Galway), showing the versatile were shown to exhibit interesting photo- bromoanilide). Upon initiation, the aryl activity of the chiral ESPHOS (Fig. 2) physical and electronic properties, and radical abstracts the hydrogen on the and semi-ESPHOS ligands. They were are potentially useful as dyes in laser amide, forming a new radical, which is used in Rh-catalyzed asymmetric olefin technology. Smet also discussed the use then capable to cyclize. Excellent yields hydroformylation, Pd-catalyzed asym- of diketopyrrolopyrroles as fluorophores were obtained in these cases [10]. metric allylic substitution and amination, for calcium ion sensors [7]. Andreas Gansauer (University of and in eu-catalyzed conjugate addition Also interesting was the work pre- Bonn, Germany) showed how epoxides of organozinc compounds to enones [5]. sented by Reko Leino (Abo Academy, could be very efficient radical precursors Finland). Solid support chemistry is usu- when treated with a titanocene dichloride Ph ally carried out on polymeric matrices catalyst, in the presence of a stoichiomet- (e.g. polystyrene beads), prepared by ric reductant. Such ~-a]koky radicals can grafting or co-polymerizing with the then add to olefins or a,~-unsaturated es- molecule of interest. The drawbacks of ters. Tethering the radical acceptor to the this approach are poor thermal stability epoxide allowed the formation of oxy- and low mechanical resistance. Other gen- and nitrogen-containing polycyclic Ph types of solid supports lacking these heterocycles [11]. ~ !J drawbacks are the fibrous polymers. Titanium complexes were also central These fibers (of length up to 2 mm) can to the research presented by Olivier ESPHOS be exposed to an electron beam generat- Riant (Universite Catholique de Louvain, ing radicals able to react with the suitable Belgium), but this time for asymmetric Fig. 2 modifier. This technology is already rou- catalysis, as salen-type complexes. These tinely used for textile processing. A spec- easily prepared, air-stable complexes The first part of the Thursday morn- tacular example was the immobilization were able to catalyze the asymmetric pi- ing session was concluded by an interest- of a TADDOL-ligand by this technique. nacol coupling of aldehydes, in excellent ing lecture from Peter Langer (Universi- This solid catalyst was then tested on the diastereoselectivity (90%), and encour- ty of Gottingen, Germany), focusing on enantioselective addition of diethylzinc aging enantioselectivity (up to 77% ee). the regio- and stereoselective cyclization to benzaldehyde in the presence ofTi(rv). Riant then went on to discuss the hydrosi- of dianions with dielectrophiles. The ele- The enantiomeric ratio of 97:3 was con- lation of ketones with triphenylsilane, in gance of the concept resides in its appar- stant, even after several cycles [8]. the presence of copper fluoride. When a ent simplicity. However, making it a re- Christian Bochet (University of Ge- binaphthyl-derived chiral ligand was gia- and stereoselecti ve reaction is by no neva) closed the morning session, in a used, enantioselectivities went up to 80% means trivial. For example, the dianion lecture dealing with the selective activa- ee. Such a transformation was found to of ethyl acetoacetate cleanly reacted with tion of functional groups using mono- be very practical, and no protection from the bis-Weinreb amide derived from chromatic light. In this approach, the se- air and moisture is required. oxalic acid, to give an y-alkylidene-a-hy- lectivity does not arise from elements After the coffee break, Goran Hil- droxybutenolide with a geometric purity contained in the substrate or the reagent, mersson (University of Goteborg, Swe- greater than 98% (E). On the other hand, but from the wavelength of a monochro- den), detailed the addition of chiral ami- the related bis-silylenolether reacted with matic light beam. The clean and smooth noethers to butyllithium, forming Cz- diacetyl in the presence of titanium tetra- orthogonal deprotection of photosensi- symmetric amide dimers in diethylether chloride to give a highly functionalized tive protecting groups was shown as an solution. The addition of THF broke cyc1opentenone (Scheme 1). Langer went example [9]. these aggregates, and only monomers on to describe the reaction of l,l-dian- The afternoon session was opened by were detected by Li-NMR. Semi-empiri- ions with the same type of 1,2-dielec- John Storey (University of Kingston, cal calculation at the PM3 level, NMR trophile leading to complex heterocyclic UK). He presented his recent results on study and structure/activity analysis structures [6]. the preparation of oxindoles and spiro- complemented these studies. In a second The second part of the morning was oxindoles by radical cyclization. The part, Hilmersson examined the properties dedicated to more multidisciplinary as- classical approach, which involves the of I-lithioacetonitrile. Indeed, these com- pects of organic synthesis, in particular cyclization of a-bromoanilides, has been pounds are known to show an imide char- with the contribution of Mario Smet shown to give poor yields of oxindoles. acter, where the metal is mainly located (University ofLeuven, Belgium), dealing Storey was able to use a very elegant rad- on the nitrogen atom. So the question arose: why a chirallithium modifier (e.g. o an aminoether) can lead to significant o asymmetric induction when located so )ly far away from the reacting center? Hil- TMSO OTMS mersson embarked on a program to an- o OEt swer this question [12]. ~OEt Asymmetric catalysis was also at the center of the lecture of Henri Doucet (Universite de Marseille, France). In- deed, palladium-catalyzed reactions fre- quently suffer from a quite low turnover Scheme 1 number, because of the precipitation of CONFERENCE REPORT 734 CHI MIA 2001,55, No.9 colloidal zerovalent palladium (so-called of a trisubstituted olefin into an internal asymmetric induction (routinely greater 'black out'). Strongly bound phosphine acetylene upon treatment with sodium ni- than 90% ee). Thorhauge went on to de- ligands can potentially prevent this event trite and acetic acid. Careful examination scribe the enantioselective Friedel-Crafts occurring, but also hinder the efficiency of the mechanism and preparation of alkylation. As an example, he showed of the catalysis. Doucet solved this prob- some of the intermediates led to the that indoles could react with a-ke- lem by preparing a cyclic tetraphosphine development of a general synthesis of toenones in the presence of the Cu-bis- (Tedicyp) (Fig. 3). When used in Pd-cat- acetylenes, reacting isoxazolinones with oxazoline catalyst. In the last part of his alyzed reactions (Heck reaction, Suzuki sodium nitrite and acetic acid in the pres- talk, Thorhauge discussed a strange re- couplings, malonate allylation), extra- ence of iron sulfate. The lecture was con- versal in the sense of asymmetric induc- ordinary turnover numbers were ob- cluded with a new procedure for prepar- tion in the Diels-Alder reaction, similar served, up to 10 billion [13]. ing esters, under totally neutral condi- to the one described in the previous lec- tions (Scheme 2). Indeed, simple heating ture. High-level calculation and screen- of an acid and a propargylic xanthate al- ing of metallic cations shed some light on lowed the clean formation of esters; in the nature of the reversal. Although still Ph2P~ (~Ph2 fact, any HX was found to work, from at a preliminary stage, this work showed that the t-Bu-substituted bis-oxazolinel Ph PPh2 hydrofluoric acid to phenol [15]. The sunny Friday morning session, Cu(n) complex is fairly rigid (but neither 2m chaired by Varinder Aggarwal, was tetrahedral nor square-planar), whereas opened by a most interesting lecture from the phenyl-substituted analogue is more Tedycip Martin Hiersemann (Technical Univer- flexible [17]. sity of Dresden, Germany), on the metal- The world of antitumor alkaloids was Fig. 3 catalyzed Claisen rearrangement. The then explored by Maria-Joao Queiroz thermal rearrangement of allyl-vinyl (University of Minho, Portugal), show- Concluding the session, Richard ethers (achiral substrate), cleanly gives a ing all the efforts of her team to assemble Grainger (King's College, London, UK), single diastereoisomer of a chiral com- the skeleton of pyrocarbazoles, such as exposed his efforts to harness the power pound, but in its racemic form. Clearly, ellipticine or olivacine. These structures of sulfur monoxide in Diels-Alder reac- this was an opportunity for asymmetric owe their potent activity to their ability to tions. Although sulfur dioxide is very catalysis. Precedents from literature intercalate in DNA and their interaction well mastered, sulfur monoxide is ex- showed that Lewis-acidic transition met- with DNA-topoisomerase II. An original tremely unstable, and has to be generated als were able to promote the reaction, combination of reductive or Heck-type in situ. Grainger systematically explored even enantioselectively, but always by intramolecular cyclizations and transi- all the possible ways to generate it. Orga- using stoichiometric amounts of chiral tion-metal catalyzed C-N bond-forming nometallic catalysis, and photochemistry ligands. In order to solve this problem, reactions was used to access the thieno- were attempted, generally with some suc- Hiersemann first studied the factors gov- carbazole system, another interesting and cess, but never in quantitative yields. It erning the selectivity, and in particular potentially active analogue [18]. was finally by thermolysis of a novel tri- the influence of the double bonds on the The second part of the morning con- sulfide-oxide that Diels-Alder trapping diastereoselectivity. He then found that tinued with a breathtaking plenary lecture of SO occurred in up to 100% yield. This the use of copper triflate in the presence by Erik Carreira (ETH Zurich). He fo- work nicely showed that perseverance of a chiral bis-oxazoline, allowed the re- cused on the zinc triflate-catalyzed addi- coupled with careful mechanistic studies action to proceed with up to 88% e.r., tion of terminal alkynes to nitrones and and X-ray analysis could solve apparent- even using catalytic amounts. Interest- aldehydes. The elegance and efficiency ly insoluble problems [14]. ingly, changing the substituents on the of this process is the underlying C-H ac- The evening plenary lecture was bril- bis-oxazoline could reverse the major tivation, leading to an atom-economical liantly delivered by Samir Zard (Ecole enantiomer obtained [16]. transformation (i.e. all the atoms of the Poly technique, Palaiseau, France). He The catalytic activity of copper/bis- reactants are included in the products); started with the total synthesis of a tetra- oxazoline complexes was further devel- this reaction does not generate any waste. cyclic alkaloid, the 13-deoxy-serratine. oped by Jacob Thorhauge (University of This is a major goal for the incoming cen- His approach (twelve steps) was three Aahrus, Denmark), in a very lively lec- tury. Not satisfied with this achievement times shorter than the only existing syn- ture. These complexes were capable of however, Carreira rendered the process thesis, with an overall yield about a thou- catalyzing the hetero Diels-Alder con- asymmetric. By using N-methylephe- sand times greater. Zard continued with densation of electron-rich alkenes with drine as a ligand, very high enantiomeric the observation of the strange conversion a-ketoenones, with an extremely high excesses could be obtained [19] (Scheme 3). The morning session was concluded by Philippe Bertus (University of Reims-Champagne-Ardenne, France), who talked about an interesting ketone cyclo- propanation reaction, in which the addi- tion of a zirconacyclopropane complex to enones and subsequent treatment with R'eOOR sulfuric acid (or a Lewis acid) cleanly af- R'COOH forded viny1cyclopropanes. The versatili- ty of this functional group in reacting fur- Scheme 2 ther in a number of different reactions CONFERENCE REPORT 735 CHIMIA 2001,55, No.9

reactions using chiral N-acylated oxaziri- NEt3 dines. His systems were able to transfer o Zn(OTfb OH ureas with very high diastereoselectivi- ties [25]. )1 + ---R' Ph Me•• Bernd Schmidt (University of Dort- R RA~ mund, Germany) closed this afternoon H - ~R' session, in a lecture focusing on the use HO NMe2 of Grubbs-type catalysts to form cyclic ethers by ring-closing metathesis. The re- Scheme 3 sidual double bond was shown to be a versatile handle to introduce further hy- makes this process particularly desirable both cases, very high ees were obtained droxyl groups and to prepare C-glyco- [20]. [22]. sides. A broad variety of these structures The afternoon session was chaired by Dario Bassani (University of Bor- could hence be accessed in a very effi- Samir Zard, and started with the presen- deaux, France) opened the final session cient process [26]. tation by Alison Franklin (University of of the day with a completely different The final day was opened by Floris Exeter, UK), fOl;:using on the preparation field, in an exciting lecture on supramo- van Delft (University of Nijmegen, Neth- of nitroalkenes. Nitroalkenes are valu- lecular photochemistry. It is known that erlands) showing his recently initiated able building blocks, due to their Michael- the photochemical dimerization of cinna- work, at the interface of organic chemis- acceptor properties, and by the possibili- mates is not very efficient, and not partic- try and biochemistry. ty of reducing the N02 function down to ularly selective (many of the possible Gilles Alcaraz (University of Rennes, an amine. Franklin found that a Horner- stereoisomers are obtained). On the other France) was next, and he showed the ap- Emmons type reaction of a nitrophospho- hand, by ordering the reactants through plications of resin-capture-release strate- nate to benzaldehyde efficiently yielded hydrogen-bonding with a suitable tem- gy in the immobilization of boronates. In substituted nitroalkenes, and systemati- plate, real supramolecular catalysis oc- this approach, an arylboronic acid is cap- cally optimized the parameters. She then curs. A ten-fold acceleration factor was tured by an ammonium resin. This ion examined their hydrogenation to yield observed, with perfect stereoselectivity pair is stable, and shows no leaching, alkylamines, first using Wilkinson's cat- [23]. even after continuous extraction with alyst, then switching to the asymmetric Jean-Michel Brunei (University of THF. On the other hand, the treatment of version. The use of a ruthenium-BINAP Marseille, France) continued, by show- this resin with an aryl halide and a Pd- catalyst gave an enantiomeric excess of ing the preparation and the use of new catalyst allowed the clean formation of 25%. Interestingly, this quite sluggish re- chiral o-hydroxyarylphosphine oxides in biphenyls via a Suzuki coupling. Very action was greatly accelerated by micro- asymmetric catalysis (Fig. 4). This ligand nice examples of macrocyclic biaryls waves [21]. was very effective, not only in the addi- were prepared by this method [27]. Carsten Schmuck (University of Co- tion of diethylzinc to benzaldehyde, but We remained in the world of transi- logne, Germany) continued with the syn- also in the asymmetric formation of ben- tion-metal catalyzed cross-coupling reac- thesis of new artificial aminoacids as zaldehyde cyanohydrin. The free phenol tions with Amadeu Brigas (University of building blocks for peptide receptors. By can be methylated, leading to a new lig- Algarve, Portugal). He detailed the use of studying the ability of Vancomycin to and, which was particularly effective in non-conventional leaving groups for Ni- specifically recognize the L-Lys-D-Ala- the asymmetric opening of epoxides by catalyzed coupling of Grignard reagents D-Ala sequence in bacteria proteins with tetrachlorosilane [24]. with aryl ethers, using tetrazoles or phe- molecular modeling, it became apparent nolderivatives[28]. that the assembly of a cyclotribenzylene Jerome Lacour (University of Gene- aminoacid, D-valin and a guanidinium RO va) demonstrated the power of helicoidal aminoacid could behave similarly. Hence, TRISPHAT anions (Fig. 5) as chiral re- Schmuck detailed his efforts towards the solving agents (for chiral cationic com- preparation of the unusual cyclotriben- plexes, such as [Fe(4,4'-Me2bpYh]2+), or zylene. Whereas the unsubstituted parent as NMR shift reagents. A new modifica- ring was relatively unproblematic, the tion, the chiral binaphthol-derived BIN- preparation of a monosubstituted cyclo- PHAT (Fig. 5) was also described, allow- tribenzylene proved to be a tough chal- ing the induction of asymmetry in config- lenge. Fig. 4. R=H, Me urationally labile monomethinium dyes The next lecture was delivered by [29]. Adriaan Minnaard (University of Gron- Alan Armstrong (Imperial College, Sandra Jonsson (University of ingen, Netherlands), who exploited the London, UK) then exposed his latest re- Stockholm, Sweden) continued with a efficient enantioselective addition of di- sults in the asymmetric transfer of hetero- fascinating lecture on the dihydroxyla- ethylzinc to enones under Cu catalysis atoms to SP2 carbons. In particular, he tion of olefins using hydrogen peroxide to prepare building blocks for asymmet- showed how substituted bicyclo[3.2.1] as a stoichiometric oxidant. She detailed ric synthesis. The well-known Feringa octanones could be efficient catalysts for the complex intertwined catalytic cycles ligand was used in nice examples of de- oxone-mediated alkene epoxidations. He involving the hydrogen peroxide oxidiz- symmetrization of meso-dienones. The demonstrated in great detail how the ing a flavin, itself oxidizing NMM into powerful asymmetric induction was also substitution pattern could influence the NMO, which then o~idized osmium to exemplified by the reaction with chiral enantioselectivities. Armstrong went on dihydroxylate the olefin (Scheme 4). racemic enones, in kinetic resolution. In to describe asymmetric nitrogen transfer Even more impressively, an asymmetric CONFERENCE REPORT 736

CHIMIA 2001. 55. No.9

CI [8] S. Degni, C.E. Wilen, R. Leino, Org. Lett. 2001,3,2551-2554. CI~CI [9] e.G. Bochet,Angew. Chern. Int. Ed. 2001, 40,2071-2073. [10] J.M.D. Storey', Tetrahedron Lett. 2000, CI aVe I 41,8173-8176. [11] A. Gansauer, H. Bluhm, Chern. Rev. 2000, CIVO...r "'"1-"..,....0 100,2771-2788. I "'F?"" [12] G. Hilmersson, O. Davidsson, J. Org. CI ~ 0/1"0 Chern. 1995,60, 7660-7669; P.I. Arvids- son, O. Davidsson, G. Hilmersson, Tetra- CI ~CI hedron Asyrn. 1999, 10, 527-534; G. Hilmersson, Chern. Eur. J. 2000,6, 3069- 3075. f1-TRISPHAT CI~CI [13] D. Laurenti, M. Feuerstein, G. Pepe, H. CI Doucet, M. Santelli, J. Org. Chern. 2001, 66, 1633-1637. Fig. 5 [14] R. Grainger, submitted for publication. [15] M. Faure-Tromeur, S.Z. Zard, Tetrahe- dron Lett. 1998, 39, 1301-1304. [16] M. Hiersemann, L. Abraham, Org. Lett. Me I 2001,3,49-52. [17] H. Audrain, J. Thorhauge, R.G. Hazell, 0 X Flavin-OOH K.A. Jorgensen, J. Org. Chern. 2000, 65, 4487-4497; K.B. Jensen, J. Thorhauge, Me" ,0- R.G. Hazell, K.A. Jorgensen, Angew. F\ X o Flavln-OH Chern. Int. Ed. 2001,40, 160-163. [18] I.C. Ferreira, M.J.R.P. Queiroz, G. Kirsch, J. Heterocyclic. Chern. 2001, in press; H.G. Herz, M.J.R.P. Queiroz, G. Maas, Scheme 4 Synthesis 1999, 1013-1016; and results to be published. [19] D.E. Frantz, R. Fassler, E.M. Carreira, J. version was also developed. The addition successful, and let us hope that the next Arn. Chern. Soc. 2000, 122, 1806-1807. Eur. of the Sharpless ligand (DHQD2PHAL), one will occur very soon. [20] V. Gandon, P. Bertus, J. Szymoniak, led to ees up to 95% [30]. 1. Org. Chern. 2000, 3713-3719. [21] A.S. Franklin, Synlett 2000, 1154-1156. Nico Margiotta (University of Bari, Received: August 15,2001 [22] R. Imbos, A. J. Minnaard, B.L. Feringa, Italy) completely changed the field in the Tetrahedron 2001, 57, 2485-2489; R. final lecture, and showed a new approach Naasz, L.A. Arnold, A. J. Minnaard, B.L. for cancer chemotherapy. It is indeed General References Feringa, Angew. Chern. Int. Ed. 2001, 40, known that some cancers have a viral or- [1] B. Goldfuss, M. Steigelmann, F. Romin- 927-930. igin or are virus-related. Hence, it is legit- ger, Eur. J. Org. Chern. 2000, 1785-1792; [23] D.M. Bassani, V. Darcos, S. Mahony, J.P. B. Goldfuss, M. Steigelmann, F. Ro- imate to try targeting both the tumor and Desvergne 1. Arn. Chern. Soc. 2000, 122, minger, Angew. Chern. Int. Ed. 2000, 39, 8795-8796. viruses by a single drug. This strategy 4133-4136. [24] S. Reymond, O. Legrand, J.M. BruneI, G. was adopted by Margiotta, who showed [2] K.C. Nicolaou, P.M. Pihko, N. Diedrichs, Buono, Eur. J. Org. Chern. 2001, 2819- hybrid compounds, derived from cispla- N. Zou, F. Bernal, Angew. Chern. Int. Ed. 2823. J.M. Brunei, O. Legrand, S. Rey- tin (currently used as antitumor) and 2001,40,1262-1265. mond, G. Buono, Angew. Chern. Int. Ed. acyclovir/penciclovir (antiviral). Inter- [3] V.K. Aggarwal, A. Alonso, G. Hynd, 2000,39,2554-2557. estingly, these compounds exhibited good K.M. Lydon, M.J. Palmer, M. Porcelloni, [25] A. Armstrong, B.R. Hayter, Chern. Cornrn. 1.R. Studley, Angew. Chern. Int. Ed. 2001, activity against HIV, but also good cyto- 1998,621; A. Annstrong, M.A. Atkin, S. 40, 1430-1432; V.K. Aggarwal, E. Alon- Swallow, Tetrahedron Lett. 2000, 41, toxicity. This is promising for a simulta- so, G. Fang, M. Ferrara, G. Hynd, M. Por- 2247-2251. neously treating viral diseases and tu- celloni, Angew. Chern. Int. Ed. 2001, 40, [26] B. Schmidt, Org. Lett. 2000, 2, 791-794; mors [31]. 1433-1436. For a general review, see: B. Schmidt, H. Wildemann, Eur. J. Org. A few words by the conference chair- A.H. Li, L.X. Dai, V.K. Aggarwal, Chern. Chern. 2000, 3145-3163. man, Prof. Philippe Renaud, concluded Rev. 1997,97,2341-2372. [27] V. Lobregat, G. Alcaraz, H. Bienayme, M. this exciting workshop. In four days and [4] e. Bianchini, G. Mantovani, A. Meli, W. Vaultier,Chrorn. Cornrnun. 2001, 817-818. Oberhauser, P. Bri.iggeller,T. Stampfl, J. [28] A.F. Brigas, R.A.W. Johnstone, J. Chern. 34 lectures, the participants could get a Chern. Soc. Dalton Trans. 2001,690-698. Soc. Perkin Trans. J 2000, 1735-1739. clear overview of the high-quality organ- [5] S. Breeden, D.J. Cole-Hamilton, D.F. Fos- [29] J. Lacour, J.J. Jodry, e. Ginglinger, S. ic chemistry that is currently being car- ter, G.J. Schwarz, M. Wills, Angew. Torche-Haldimann, Angew. Chern. Int. ried out in Europe. The format chosen by Chern. Int. Ed. 2000,39,4106-4108. Ed. 1998, 37, 2379-1380; J. Lacour, A. the organizer was particularly well adapt- [6] P. Langer, T. Schneider, M. Stoll, Chern. Londez, C. Goujon-Ginglinger, V. Buss, ed to fuel the enthusiasm of hearing about Eur. J. 2000,6,3204-3214; P. Langer, T. G. Bemadinelli,Org. Lett. 2000,4185-4188. such a broad range of topics. The fact that Krummel, Chern. Eur. J. 2001, 7, 1720- [30] K. Bergstad, S.Y. Jonsson, J.E. Backvall, 1727; P. Langer, E. Holtz, Angew. Chern. J. Arn. Chern. Soc. 1999, 121, 10424- most of the participants were also active Int. Ed. 2000, 39, 3086-3090; P. Langer, 10425; S. Jonsson, K. Farngardh, J.E. lecturers also contributed to keep the in- T. Eckardt, Angew. Chern. Int. Ed. 2000, Backvall, J. Arn. Chern. Soc. 2001, 123, terest during the question sessions, meals 39, 4343-4346. 1365-1371. and late-night discussions. There are no [7] M. Smet, J. Van Dijk, W. Dehaen, Synlett [31] N. Margiotta, F.P. Fanizzi, J. Kobe, G. Na- doubts that the future editions will be as 1999,4,495-497. tile, Eur. J. Inorg. Chern. 2001,1303-1310.